Von Willebrands Disease (vWD) is the most common inherited bleeding disorder. We have studied the efficacy and feasibility of treating a child with type III severe vWD solely with cryoprecipitate prepared by repeated DDAVP-stimulated plasma exchange donation from a single, dedicated, paternal donor. An infant presented with massive hemorrhage at circumcision. The child was found to have FVIII:C 4 percent, FVIII:Ag 20 percent, vWF:RCo 21 percent, vWF:Ag 3 percent, indicative of severe vWD. His father carried an allele with a defect at the level of vWF mRNA expression but had a negative bleeding history with normal coagulation values. Cryoprecipitate was prepared from serial DDAVP-stimulated plasma exchange donation using peripheral venous access, ACD-A anticoagulant, and autologous cryoprecipitate-depleted plasma as replacement fluid. Exchange volume was 9,620 plus or minus 2,191 (m plus or minus SD, range 4,715-13,500) ml during the first 37 plasma exchange donations that the donor made during the 13 years since the childs birth. Repeated plasma exchange donation was well tolerated, with adverse effects including mild headache and flushing due to the DDAVP, and citrate toxicity. Cryoprecipitate was stored for less than 1 to 102 months at minus 70 (C. 90 percent of the cryoprecipitate was transfused after 1 year of storage, with a mean collection to transfusion interval of 2.4 years. Cryoprecipitate tested after 13 to 77 months of storage showed 48 to 124 percent of the original FVIII activity; decreased activity was noted with increasing length of storage. Over 13 years, 114,309 units of FVIII were collected in this manner. Most recently, we have standardized plasma exchange donation to involve processing of exactly 4,500 ml of plasma, which yields a mean of 14 bags of cryoprecipitate, each having a FVIII content of 262 plus or minus 62 units). Manufacture of plasma exchange donation-derived FVIII resulted in an estimated 50 percent cost reduction compared with similar doses of commercial factor concentrates. All bleeding episodes that occurred in the patient since birth were successfully managed with cryoprecipitate derived by this method. Remarkably, at age 13, the child has received only one donor exposure throughout his entire life, that of the paternal donor of his cryoprecipitate. Cryoprecipitate prepared by repeated plasma exchange donation of a vWD carrier provided excellent hemostatic function, even after prolonged storage intervals of greater than 1 year. Plasma exchange donation of a committed donor may be the safest option for long-term management of vWD, and provides a cost-effective alternative to commercial factor concentrates.